Recently developed imaging technologies can locate cancer that is hiding in the body, and thus the cancer can be removed by several methods, such as radiation irradiation and endoscopy operation. However, even though the exact location of the cancer is found, the surgical exclusion of the cancer is impossible due to several reasons, such as the cancer spreading out all over the whole organ or adjoining to another organ. Liver cancer, pancreatic cancer, or the like, even though detected, cannot be radically cured through surgical operation.
Currently, transarterial chemoembolization (TACE), which is most commonly done in the treatment of a liver tumor, is a treatment wherein an anticancer drug is administered to the artery, which supplies nutrition to the liver tumor, and then the blood vessel is blocked. Liver tissues receive oxygen and nutrients through the portal vein, which turns around the small intestine and large intestine, and the hepatic artery, which comes out directly from the main artery. Normal liver tissues mainly receive blood from the portal vein, and the tumor tissues mainly receive blood from the hepatic artery. Therefore, in cases where an anticancer drug is administered to the hepatic artery, which supplies nutrition to the tumor, and then the blood vein is blocked, only the tumor can be selectively necrotized without harming normal liver tissues. Such a treatment has many advantages, such as having no restrictions according to the progression of cancer and thus having a wide range of applications, and having a few limitations in the objects of the treatment, and thus currently makes a large contribution on the improvement in the cure rate of the liver cancer. As for chemoembolization, a catheter is first inserted into the femoral artery in the groin and approaches the hepatic artery, and then a vascular contrast medium is injected to obtain information necessary for the treatment, such as positions, sizes, and blood supply aspects of tumors. When the treatment protocol is decided, a thin tube with a thickness of about 1 mm is inserted into the catheter, and then the artery to be targeted is found, followed by surgical operation.
Currently, representatively, hepatic embolization using lipiodol has been clinically applied most frequently, and a significant number of patent technologies using the hepatic embolization have also been reported. Lipiodol contains a lot of iodine as a constituent element, and thus allows CT imaging, thereby providing a convenient surgical procedure. However, in order to load doxorubicin, an injection in which a drug is dissolved needs to be shaken and mixed with oily lipiodol immediately before the surgical operation. In addition, it has been clinically reported that after the surgical operation, the doxorubicin dissolved in an aqueous phase does not accumulate in the liver cancer site, but promptly leaks into the body blood, thereby failing to obtain a sufficient anticancer effect and causing a considerable side effect to patients.
U.S. Pat. No. 7,442,385 discloses a method wherein, after polyvinylalcohol (PVA) is cross-linked to prepare micro-sized particles, doxorubicin as a cancer drug is adsorbed onto a surface of beads via an electric attraction and then transferred to the liver cancer site, thereby attaining both a sustained release of anticancer drug and an embolization effect. For achieving this, during a cross-linkage procedure of polyvinylalcohol, 2-acrylamido-2-methylpropane sulfonic acid (AMPS), which is an anionic monomer, is covalently linked to the end of the cross-linkage to modify the polymer, thereby allowing the polymer to adsorb a cationic drug, such as doxorubicin. However, according to the hepatic embolization using polyvinylalcohol, cross-liked PVA does not degrade in the body, and thus, after the necrotization of the liver tumor, PVA beads were irregularly diffused in the body, causing an inflammation or more unfortunately, the PVA beads go down the blood vessel and spreads into another organ, causing cerebrovascular disease. Therefore, a drug delivery system capable of achieving both a function as an anticancer drug carrier and a vascular embolization function to solve the foregoing problems is required.
Due to these requirements, the present inventors have developed albumin/dextran sulfate beads (Korean Patent Application No. 10-2013-0139303) and albumin/glycosaminoglycan beads (Korean Patent Application No. 10-2013-0139304), which solved problems of existing microbeads for cancer local treatment. The microbeads are safe to the human body when applied to the human body since the microbeads are prepared from albumin, as a biocompatible material, and an anionic polymer, and can effectively inhibit the growth of tumors by effectively blocking the blood vessel that supplies nutrients to the liver tumor and can continuously release an anticancer drug adsorbed onto the surfaces of the beads.
Meanwhile, the drug release characteristics of microbeads for transarterial chemoembolization are different for the respective beads, and, due to a small amount of clinical results, statistic results showing whether a fast release rate is more effective or a slow release rate is more effective are insufficient. Further, the drug release rate also needs to be controlled depending on the size of tumors and the progression of cancers.
Throughout the entire specification, many papers, and patent documents are referenced and their citations are represented. The disclosure of the cited papers and patent documents are entirely incorporated by reference into the present specification, and the level of the technical field within which the present invention falls and the details of the present invention are explained more clearly.